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The Nuclear Orphan Receptor NR2F6 Is a Central Checkpoint for Cancer Immune Surveillance
Nuclear receptor subfamily 2, group F, member 6 (NR2F6) is an orphan member of the nuclear receptor superfamily. Here, we show that genetic ablation of Nr2f6 significantly improves survival in the murine transgenic TRAMP prostate cancer model. Furthermore, Nr2f6(−/−) mice spontaneously reject implan...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594157/ https://www.ncbi.nlm.nih.gov/pubmed/26387951 http://dx.doi.org/10.1016/j.celrep.2015.08.035 |
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author | Hermann-Kleiter, Natascha Klepsch, Victoria Wallner, Stephanie Siegmund, Kerstin Klepsch, Sebastian Tuzlak, Selma Villunger, Andreas Kaminski, Sandra Pfeifhofer-Obermair, Christa Gruber, Thomas Wolf, Dominik Baier, Gottfried |
author_facet | Hermann-Kleiter, Natascha Klepsch, Victoria Wallner, Stephanie Siegmund, Kerstin Klepsch, Sebastian Tuzlak, Selma Villunger, Andreas Kaminski, Sandra Pfeifhofer-Obermair, Christa Gruber, Thomas Wolf, Dominik Baier, Gottfried |
author_sort | Hermann-Kleiter, Natascha |
collection | PubMed |
description | Nuclear receptor subfamily 2, group F, member 6 (NR2F6) is an orphan member of the nuclear receptor superfamily. Here, we show that genetic ablation of Nr2f6 significantly improves survival in the murine transgenic TRAMP prostate cancer model. Furthermore, Nr2f6(−/−) mice spontaneously reject implanted tumors and develop host-protective immunological memory against tumor rechallenge. This is paralleled by increased frequencies of both CD4(+) and CD8(+) T cells and higher expression levels of interleukin 2 and interferon γ at the tumor site. Mechanistically, CD4(+) and CD8(+) T cell-intrinsic NR2F6 acts as a direct repressor of the NFAT/AP-1 complex on both the interleukin 2 and the interferon γ cytokine promoters, attenuating their transcriptional thresholds. Adoptive transfer of Nr2f6-deficient T cells into tumor-bearing immunocompetent mice is sufficient to delay tumor outgrowth. Altogether, this defines NR2F6 as an intracellular immune checkpoint in effector T cells, governing the amplitude of anti-cancer immunity. |
format | Online Article Text |
id | pubmed-4594157 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-45941572015-10-28 The Nuclear Orphan Receptor NR2F6 Is a Central Checkpoint for Cancer Immune Surveillance Hermann-Kleiter, Natascha Klepsch, Victoria Wallner, Stephanie Siegmund, Kerstin Klepsch, Sebastian Tuzlak, Selma Villunger, Andreas Kaminski, Sandra Pfeifhofer-Obermair, Christa Gruber, Thomas Wolf, Dominik Baier, Gottfried Cell Rep Article Nuclear receptor subfamily 2, group F, member 6 (NR2F6) is an orphan member of the nuclear receptor superfamily. Here, we show that genetic ablation of Nr2f6 significantly improves survival in the murine transgenic TRAMP prostate cancer model. Furthermore, Nr2f6(−/−) mice spontaneously reject implanted tumors and develop host-protective immunological memory against tumor rechallenge. This is paralleled by increased frequencies of both CD4(+) and CD8(+) T cells and higher expression levels of interleukin 2 and interferon γ at the tumor site. Mechanistically, CD4(+) and CD8(+) T cell-intrinsic NR2F6 acts as a direct repressor of the NFAT/AP-1 complex on both the interleukin 2 and the interferon γ cytokine promoters, attenuating their transcriptional thresholds. Adoptive transfer of Nr2f6-deficient T cells into tumor-bearing immunocompetent mice is sufficient to delay tumor outgrowth. Altogether, this defines NR2F6 as an intracellular immune checkpoint in effector T cells, governing the amplitude of anti-cancer immunity. Cell Press 2015-09-17 /pmc/articles/PMC4594157/ /pubmed/26387951 http://dx.doi.org/10.1016/j.celrep.2015.08.035 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Hermann-Kleiter, Natascha Klepsch, Victoria Wallner, Stephanie Siegmund, Kerstin Klepsch, Sebastian Tuzlak, Selma Villunger, Andreas Kaminski, Sandra Pfeifhofer-Obermair, Christa Gruber, Thomas Wolf, Dominik Baier, Gottfried The Nuclear Orphan Receptor NR2F6 Is a Central Checkpoint for Cancer Immune Surveillance |
title | The Nuclear Orphan Receptor NR2F6 Is a Central Checkpoint for Cancer Immune Surveillance |
title_full | The Nuclear Orphan Receptor NR2F6 Is a Central Checkpoint for Cancer Immune Surveillance |
title_fullStr | The Nuclear Orphan Receptor NR2F6 Is a Central Checkpoint for Cancer Immune Surveillance |
title_full_unstemmed | The Nuclear Orphan Receptor NR2F6 Is a Central Checkpoint for Cancer Immune Surveillance |
title_short | The Nuclear Orphan Receptor NR2F6 Is a Central Checkpoint for Cancer Immune Surveillance |
title_sort | nuclear orphan receptor nr2f6 is a central checkpoint for cancer immune surveillance |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594157/ https://www.ncbi.nlm.nih.gov/pubmed/26387951 http://dx.doi.org/10.1016/j.celrep.2015.08.035 |
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